Whipple’s disease- Causes, Complications, and Treatment

Definition

Whipple’s disease is a multi-system infectious bacterial disease that interferes with the body’s ability to metabolize fats. Caused by the bacterium Tropheryma whipplei, the disorder can affect any system in the body, including the brain, eyes, heart, joints, and lungs, but usually occurs in the gastrointestinal system. Neurological symptoms occur in up to 40 percent of individuals and may include dementia, abnormalities of eye and facial muscle movements, headaches, seizures, loss of muscle control, memory loss, weakness, and vision problems.

Gastrointestinal symptoms may include diarrhea, weight loss, fatigue, weakness, and abdominal bleeding and pain. Fever, cough, anemia, heart and lung damage, darkening of the skin, and joint soreness may also be present. The disease is more common in men and neurological symptoms are more common in individuals who have severe abdominal disease, Rarely, neurological symptoms may appear without gastrointestinal symptoms and can mimic symptoms of almost any neurologic disease.

The small intestine has a ridged lining covered with tiny fingerlike projections called villi

Epidemiology

International statistics

Whipple disease is extremely rare worldwide; only several hundred clinical cases have been reported, mostly from North America and western Europe. The disease appears to be associated with the human leukocyte antigen B27 (HLA-B27) haplotype. The incidence has been estimated to be less than 1 per 1,000,000.

Race, sex and age-related demographics

Whipple disease is most common in white males and rarely is described in females (male-to-female ratio: approximately 8-9:1). The route of disease transmission is not known but may be associated with occupational exposure to animals and soil. Whipple disease is usually observed in middle-aged and elderly persons (older than 40 y).

Whipple’s disease risk factors

Factors that can increase the risk of Whipple’s disease are not well known since so little is known about the bacterium that causes the disease in the first place. Based on some research findings, it appears more likely to affect:

• Men
• Individuals among the ages of 40 and 60
• Individuals of Caucasian race in North America and Europe

Causes of Whipple’s disease

Whipple’s disease is caused by the bacteria Tropheryma whipplei. It is a gram-positive bacterium. These bacteria affect the gastrointestinal tract and lead to the thickening of tissues. The bacteria infiltrates within macrophages in the mucosal lining of the small intestine.

It also affects microvilli lining the small intestine. These villi become abnormally widened and flattened because of densely packed macrophages. Villi help in the absorption of nutrients, but as in this condition, villi are affected; there is impairment in the absorption of nutrients, fats, and carbohydrates.

Symptoms of Whipple’s disease

This disease can affect many parts of the body. The small intestine is the main organ affected. Symptoms usually begin slowly and occur in stages. The first stage includes:

• Pain in the joints (in 90% of cases)
• Fever

The disease is usually not diagnosed until several years later when additional symptoms may develop. These include:

• Pain and bloating in the abdomen
• Diarrhea
• Fatty, foul-smelling stools
• Bleeding from the intestines
• Weight loss
• Weakness
• Fatigue (often from anemia )
• Cough and chest pain
• Increased skin pigmentation (in 50% of cases)
• Swollen lymph glands

Skin lesions in Whipple disease

If the disease is not treated, this second stage may last for a number of years. Then, more severe symptoms may occur due to the lack of nutrients reaching different parts of the body. Symptoms may occur in any part of the body, but most likely the heart, nervous system, brain, lungs, eyes, or skin. If the disease still is not treated, it usually causes death in this third stage.

Whipple’s disease complications       

Complications may include:

• Brain damage
• Heart valve damage (from endocarditis)
• Nutritional deficiencies
• Symptoms return (which may be because of drug resistance)
• Weight loss

Diagnosis and test

The process of diagnosing Whipple disease typically includes the following tests:

Physical exam: Your doctor will likely begin with a physical exam, looking for signs and symptoms that suggest the presence of this condition, such as abdominal tenderness and skin darkening, particularly on sun-exposed parts of your body.

Biopsy: An important step in diagnosing Whipple disease is taking a tissue sample (biopsy), usually from the lining of the small intestine. To do this, your doctor typically performs an upper endoscopy. The procedure uses a thin, flexible tube (scope) that passes through your mouth, throat, windpipe and stomach to your small intestine. The scope allows your doctor to view your digestive passages and take tissue samples.

Blood tests: Your doctor may also order blood tests, such as a complete blood count. Blood tests can detect certain conditions associated with Whipple disease, particularly anemia, which is a decline in the number of red blood cells, and low concentrations of albumin, a protein in your blood.

Treatment and medications

Whipple’s disease is treated with antibiotics to fight the bacteria. Intravenous (IV) antibiotics are prescribed initially followed by oral antibiotics.

• IV antibiotics such as penicillin G, streptomycin, and ceftriaxone can be prescribed for 10 to 15 days as initial therapy.
• Oral antibiotics such as sulphamethoxazole-trimethoprim are prescribed for 1 to 2 years as maintenance therapy.
• Sulfonamides such as sulphamethoxazole can cross the blood-brain barrier and can be given with antimalarial drugs to treat symptoms associated with the central nervous system (brain).
• Even if the symptoms go away during the initial days of therapy, treatment should be continued until the healthcare provider advises to stop.
• Nutrient supplements such as iron, vitamin D, vitamin K, folic acid, calcium, and other mineral supplements can be prescribed to treat malnutrition and anemia.
• Intake of fluids and a high-calorie diet should be increased to improve malnutrition.
• Patients should undergo regular check-ups and follow-up testing as the disease may relapse even after receiving effective treatment. Quantitative PCR (qPCR) can be performed using feces as a sample for every 3 months.

Prevention of Whipple’s disease

Experts have not yet found a way to prevent Whipple disease.

Eating, Diet, and Nutrition

A person with Whipple disease and malabsorption may need

• A diet high in calories and protein
• Vitamins
• Nutritional supplements

People with Whipple disease should discuss their nutritional needs with a dietitian or other health care professional and meet regularly with him or her to monitor changing nutritional needs.